Evidence map›Paper›PMID 37949861›Full record

ArticleNature communications2023

A statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples.

Wenpin Hou, Zhicheng Ji, Zeyu Chen, E John Wherry, Stephanie C Hicks, Hongkai Ji

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
14.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
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  18. Pseudotimecascade Visualizes Gene Expression Cascade in Pseudotime Analysis.Computational and structural biotechnology journal · 2026
    Article
  19. Review
  20. Review

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Wenpin HouDepartment of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0003-0972-2192
Zhicheng JiDepartment of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Zeyu ChenDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
E John WherryDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Stephanie C HicksDepartment of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. shicks19@jhu.edu.ORCID 0000-0002-7858-0231
Hongkai JiDepartment of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. hji@jhu.edu.ORCID 0000-0002-6480-0141
Johns Hopkins University · USParker Institute for Cancer Immunotherapy · US

Funding

Synergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8M
Big Data Methods for Decoding Gene RegulationR01HG009518 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI JI, HONGKAI · 2018 to 2021
$1.7M
Computational tools for regulome mapping using single-cell genomic dataR01HG010889 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI JI, HONGKAI · 2019 to 2022
$1.6M
Computational Methods for Inferring Single-cell DNA Methylation and its Spatial LandscapeR00HG011468 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOU, WENPIN · 2022 to 2024
$747k
Statistical Methods for the Normalization and Quantification of Single-Cell RNA-Sequencing DataR00HG009007 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI HICKS, STEPHANIE CARINNE · 2018 to 2020
$725k
Computational Methods for Inferring Single-cell DNA Methylation and its Spatial LandscapeK99HG011468 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI HOU, WENPIN · 2021 to 2022
$168k
NHGRI NIH HHS K99 HG011468NHGRI NIH HHS R00 HG009007NHGRI NIH HHS R00 HG011468NHGRI NIH HHS R01 HG009518NHGRI NIH HHS R01 HG010889NIAID NIH HHS P01 AI108545
6 · The paper itself

Abstract

Pseudotime analysis with single-cell RNA-sequencing (scRNA-seq) data has been widely used to study dynamic gene regulatory programs along continuous biological processes. While many methods have been developed to infer the pseudotemporal trajectories of cells within a biological sample, it remains a challenge to compare pseudotemporal patterns with multiple samples (or replicates) across different experimental conditions. Here, we introduce Lamian, a comprehensive and statistically-rigorous computational framework for differential multi-sample pseudotime analysis. Lamian can be used to identify changes in a biological process associated with sample covariates, such as different biological conditions while adjusting for batch effects, and to detect changes in gene expression, cell density, and topology of a pseudotemporal trajectory. Unlike existing methods that ignore sample variability, Lamian draws statistical inference after accounting for cross-sample variability and hence substantially reduces sample-specific false discoveries that are not generalizable to new samples. Using both real scRNA-seq and simulation data, including an analysis of differential immune response programs between COVID-19 patients with different disease severity levels, we demonstrate the advantages of Lamian in decoding cellular gene expression programs in continuous biological processes.

Indexed as

Gene Expression ProfilingSingle-Cell Gene Expression AnalysisComputer SimulationHumansSequence Analysis, RNASingle-Cell Analysis

Identifiers

PMID37949861
PMCPMC10638410
OpenAlexW4388584919

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.